Cargando…
The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine
In this study we investigated the role of the circadian mechanism on cognition-relevant brain regions and neurobiological impairments associated with heart failure (HF), using murine models. We found that the circadian mechanism is an important regulator of healthy cognitive system neurobiology. Nor...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428811/ https://www.ncbi.nlm.nih.gov/pubmed/30899044 http://dx.doi.org/10.1038/s41598-019-41469-7 |
_version_ | 1783405459350224896 |
---|---|
author | Duong, Austin T. H. Reitz, Cristine J. Louth, Emma L. Creighton, Samantha D. Rasouli, Mina Zwaiman, Ashley Kroetsch, Jeffrey T. Bolz, Steffen-Sebastian Winters, Boyer D. Bailey, Craig D. C. Martino, Tami A. |
author_facet | Duong, Austin T. H. Reitz, Cristine J. Louth, Emma L. Creighton, Samantha D. Rasouli, Mina Zwaiman, Ashley Kroetsch, Jeffrey T. Bolz, Steffen-Sebastian Winters, Boyer D. Bailey, Craig D. C. Martino, Tami A. |
author_sort | Duong, Austin T. H. |
collection | PubMed |
description | In this study we investigated the role of the circadian mechanism on cognition-relevant brain regions and neurobiological impairments associated with heart failure (HF), using murine models. We found that the circadian mechanism is an important regulator of healthy cognitive system neurobiology. Normal Clock(∆19/∆19) mice had neurons with smaller apical dendrite trees in the medial prefrontal cortex (mPFC), and hippocampus, showed impaired visual-spatial memory, and exhibited lower cerebrovascular myogenic tone, versus wild types (WT). We then used the left anterior descending coronary artery ligation model to investigate adaptations in response to HF. Intriguingly, adaptations to neuron morphology, memory, and cerebrovascular tone occurred in differing magnitude and direction between Clock(∆19/∆19) and WT mice, ultimately converging in HF. To investigate this dichotomous response, we performed microarrays and found genes crucial for growth and stress pathways that were altered in Clock(∆19/∆19) mPFC and hippocampus. Thus these data demonstrate for the first time that (i) the circadian mechanism plays a role in neuron morphology and function; (ii) there are changes in neuron morphology and function in HF; (iii) CLOCK influences neurobiological gene adaptations to HF at a cellular level. These findings have clinical relevance as patients with HF often present with concurrent neurocognitive impairments. There is no cure for HF, and new understanding is needed to reduce morbidity and improve the quality of life for HF patients. |
format | Online Article Text |
id | pubmed-6428811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64288112019-03-28 The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine Duong, Austin T. H. Reitz, Cristine J. Louth, Emma L. Creighton, Samantha D. Rasouli, Mina Zwaiman, Ashley Kroetsch, Jeffrey T. Bolz, Steffen-Sebastian Winters, Boyer D. Bailey, Craig D. C. Martino, Tami A. Sci Rep Article In this study we investigated the role of the circadian mechanism on cognition-relevant brain regions and neurobiological impairments associated with heart failure (HF), using murine models. We found that the circadian mechanism is an important regulator of healthy cognitive system neurobiology. Normal Clock(∆19/∆19) mice had neurons with smaller apical dendrite trees in the medial prefrontal cortex (mPFC), and hippocampus, showed impaired visual-spatial memory, and exhibited lower cerebrovascular myogenic tone, versus wild types (WT). We then used the left anterior descending coronary artery ligation model to investigate adaptations in response to HF. Intriguingly, adaptations to neuron morphology, memory, and cerebrovascular tone occurred in differing magnitude and direction between Clock(∆19/∆19) and WT mice, ultimately converging in HF. To investigate this dichotomous response, we performed microarrays and found genes crucial for growth and stress pathways that were altered in Clock(∆19/∆19) mPFC and hippocampus. Thus these data demonstrate for the first time that (i) the circadian mechanism plays a role in neuron morphology and function; (ii) there are changes in neuron morphology and function in HF; (iii) CLOCK influences neurobiological gene adaptations to HF at a cellular level. These findings have clinical relevance as patients with HF often present with concurrent neurocognitive impairments. There is no cure for HF, and new understanding is needed to reduce morbidity and improve the quality of life for HF patients. Nature Publishing Group UK 2019-03-21 /pmc/articles/PMC6428811/ /pubmed/30899044 http://dx.doi.org/10.1038/s41598-019-41469-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Duong, Austin T. H. Reitz, Cristine J. Louth, Emma L. Creighton, Samantha D. Rasouli, Mina Zwaiman, Ashley Kroetsch, Jeffrey T. Bolz, Steffen-Sebastian Winters, Boyer D. Bailey, Craig D. C. Martino, Tami A. The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title | The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title_full | The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title_fullStr | The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title_full_unstemmed | The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title_short | The Clock Mechanism Influences Neurobiology and Adaptations to Heart Failure in Clock(∆19/∆19) Mice With Implications for Circadian Medicine |
title_sort | clock mechanism influences neurobiology and adaptations to heart failure in clock(∆19/∆19) mice with implications for circadian medicine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428811/ https://www.ncbi.nlm.nih.gov/pubmed/30899044 http://dx.doi.org/10.1038/s41598-019-41469-7 |
work_keys_str_mv | AT duongaustinth theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT reitzcristinej theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT louthemmal theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT creightonsamanthad theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT rasoulimina theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT zwaimanashley theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT kroetschjeffreyt theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT bolzsteffensebastian theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT wintersboyerd theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT baileycraigdc theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT martinotamia theclockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT duongaustinth clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT reitzcristinej clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT louthemmal clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT creightonsamanthad clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT rasoulimina clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT zwaimanashley clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT kroetschjeffreyt clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT bolzsteffensebastian clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT wintersboyerd clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT baileycraigdc clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine AT martinotamia clockmechanisminfluencesneurobiologyandadaptationstoheartfailureinclock1919micewithimplicationsforcircadianmedicine |